Bone marrow cultures and biopsy specimens are commonly obtained to rule out disseminated infections, especially in persons with the acquired immunodeficiency syndrome (AIDS) and cytopenias. Using culture as the gold standard, we reviewed 130 consecutive bone marrow cores obtained from 114 AIDS patients along with results of concurrent blood and/or bone marrow aspirate cultures to determine the usefulness of histologic examination for diagnosis of mycobacterial and fungal infections. We also compared the ability of Ziehl-Neelsen, auramine-rhodamine (AR), polyclonal antibody to Mycobacterium bovis (Ab), and Gomori's methenamine silver staining to detect infections. Twenty-seven patients had mycobacterial infection (25 Mycobacterium avium-intracellulare complex cases and two Mycobacterium tuberculosis cases) detected by blood and/or bone marrow cultures. The maximum sensitivity of histology was 50% when the auramine-rhodamine stain and the polyclonal antibody to M bovis were used in combination. The single best stain was auramine-rhodamine, with a sensitivity of 44%, followed by the polyclonal antibody to M bovis (35%). Granulomas were observed in nine cases of mycobacterial infection and did not correlate with the presence of stainable organisms. Of seven patients with positive fungal cultures of bone marrow, four had granulomas and a positive Gomori's methenamine silver stain, one had only a positive stain, and two had neither granulomas nor a diagnostic stain. Overall, granulomas were not sensitive for the detection of infections when culture-proven mycobacterial and fungal cases were evaluated together. We conclude that bone marrow examination has a limited value in the routine evaluation of common opportunistic infections in AIDS patients and recommend that less-invasive tests, such as blood cultures, be obtained initially in most circumstances.